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7 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PIP4P1
phosphatidylinositol-4,5-bisphosphate 4-phosphatase 1
Chromosome 14 · 14q11.2
NCBI Gene: 90809Ensembl: ENSG00000165782.12HGNC: HGNC:19299UniProt: Q86T03
46PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of TORC1 signalinglysosomal membranephosphatidylinositol-4,5-bisphosphate 4-phosphatase activityresponse to sterol depletionattention deficit hyperactivity disorderhereditary attention deficit-hyperactivity disorderIntellectual disability - hypotonia - spasticity - sleep disorderMODY
✦AI Summary

PIP4P1 (also known as TMEM55B) is a phosphatidylinositol-4,5-bisphosphate 4-phosphatase that catalyzes hydrolysis of PtdIns(4,5)P2 to PtdIns(4)P with high substrate specificity 1. The enzyme plays multiple critical roles in lysosomal homeostasis and cellular metabolism. PIP4P1 regulates lysosomal positioning by recruiting the adaptor protein JIP4 to lysosomal membranes, thereby inducing retrograde transport toward the cell center via dynein motor proteins 2. Additionally, PIP4P1 assembles the V-ATPase complex within lysosomal membrane lipid rafts, facilitating amino acid-dependent mTORC1 activation essential for nutrient sensing 3. PIP4P1 phosphorylation by Erk/MAPK regulates this lysosomal positioning in response to external stimuli 4. In cholesterol metabolism, PIP4P1 modulates PtdIns(4,5)P2 levels to regulate low-density lipoprotein receptor degradation in lysosomes, thereby controlling plasma cholesterol homeostasis 5. Conversely, PIP4P2 (another phosphatidylinositol-4,5-bisphosphate 4-phosphatase) positively regulates basal autophagy 6. PIP4P1 dysfunction may contribute to cleft lip/palate pathogenesis 7. These coordinated functions position PIP4P1 as a master regulator of lysosomal dynamics and metabolic signaling.

Sources cited
1
PIP4P1 catalyzes hydrolysis of PtdIns(4,5)P2 to PtdIns(4)P with high substrate specificity
PMID: 16365287
2
PIP4P1 recruits JIP4 to lysosomes, inducing retrograde dynein-dependent transport
PMID: 29146937
3
PIP4P1 assembles V-ATPase complex in lysosomal lipid rafts for amino acid-dependent mTORC1 activation
PMID: 29644770
4
PIP4P1 phosphorylation by Erk/MAPK regulates lysosomal positioning in response to stimuli
PMID: 33537719
5
PIP4P1 regulates PtdIns(4,5)P2 levels to control LDLR lysosomal degradation and plasma cholesterol
PMID: 32188273
6
PIP4P2, a related phosphatidylinositol-4,5-bisphosphate 4-phosphatase, positively regulates basal autophagy
PMID: 38880622
7
PIP4P1 polymorphisms may associate with non-syndromic cleft lip/palate susceptibility
PMID: 31261547
Disease Associationsⓘ20
attention deficit hyperactivity disorderOpen Targets
0.05Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.04Suggestive
Intellectual disability - hypotonia - spasticity - sleep disorderOpen Targets
0.04Suggestive
MODYOpen Targets
0.04Suggestive
schizophrenia 15Open Targets
0.04Suggestive
severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiencyOpen Targets
0.03Suggestive
inherited obesityOpen Targets
0.03Suggestive
obesityOpen Targets
0.03Suggestive
Phelan-McDermid syndromeOpen Targets
0.03Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
metastatic melanomaOpen Targets
0.01Suggestive
follicular lymphomaOpen Targets
0.01Suggestive
steatosisOpen Targets
0.01Suggestive
non-alcoholic steatohepatitisOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
chronic kidney diseaseOpen Targets
0.00Suggestive
atrial fibrillationOpen Targets
0.00Suggestive
Hepatic steatosisOpen Targets
0.00Suggestive
nasopharyngeal carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PIK3R3Protein interaction100%PIK3R1Protein interaction100%PIK3CBProtein interaction100%PIK3CDProtein interaction100%PIK3CAProtein interaction100%PTENProtein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
40%
Ovary
35%
Liver
30%
Heart
25%
Brain
21%
Gene Interaction Network
Click a node to explore
PIP4P1PIK3R3PIK3R1PIK3CBPIK3CDPIK3CAPTEN
PROTEIN STRUCTURE
Preparing viewer…
PDB9QM9 · 1.55 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.70LoF Tolerant
pLIⓘ
0.10Tolerant
Observed/Expected LoF0.45 [0.29–0.70]
RankingsWhere PIP4P1 stands among ~20K protein-coding genes
  • #9,360of 20,598
    Most Researched46
  • #5,294of 17,882
    Most Constrained (LOEUF)0.70
Genes detectedPIP4P1
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
Trehalose limits opportunistic mycobacterial survival during HIV co-infection by reversing HIV-mediated autophagy block.
PMID: 32079455
Autophagy · 2021
1.00
2
CRISPRa Analysis of Phosphoinositide Phosphatases Shows That TMEM55A Is a Positive Regulator of Autophagy.
PMID: 38880622
Biol Pharm Bull · 2024
0.86
3
Regulation of lysosomal positioning via TMEM55B phosphorylation.
PMID: 33537719
J Biochem · 2021
0.71
4
Phosphatidylinositol-(4,5)-Bisphosphate Regulates Plasma Cholesterol Through LDL (Low-Density Lipoprotein) Receptor Lysosomal Degradation.
PMID: 32188273
Arterioscler Thromb Vasc Biol · 2020
0.57
5
TMEM55B contributes to lysosomal homeostasis and amino acid-induced mTORC1 activation.
PMID: 29644770
Genes Cells · 2018
0.43