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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PIP
prolactin induced protein
Chromosome 7 · 7q34
NCBI Gene: 5304Ensembl: ENSG00000159763.4HGNC: HGNC:8993UniProt: P12273
147PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular exosomeaspartic-type endopeptidase activityprotein bindingIgG bindingneurodegenerative diseasechronic laryngitisdiabetic ketoacidosisAlzheimer disease
✦AI Summary

PIP (prolactin induced protein) is a 17-kDa secreted glycoprotein with diverse regulatory functions across multiple tissues 1. The protein exhibits aspartic-type endopeptidase activity, specifically degrading fibronectin, which contributes to its role in cell migration and invasion 1. PIP serves as a critical regulator of aquaporin 5 (AQP5) trafficking in salivary and lacrimal glands, where it interacts with the AQP5 C-terminus to control proper apical membrane localization 2. In corneal tissue, PIP accelerates wound healing by promoting epithelial cell and fibroblast migration while exhibiting anti-fibrotic properties through downregulation of TGF-β1, smooth muscle actin, and collagen III 3. In breast cancer, PIP is widely expressed and regulated by androgen and prolactin signaling through STAT5, Runx2, and CREB1 transcription factors 1. The protein is essential for integrin-β1 outside-in signaling activation and promotes cell proliferation and invasion in breast cancer cells 1. PIP dysfunction is associated with Sjögren's syndrome, where altered PIP expression correlates with abnormal AQP5 localization and salivary gland hypofunction 2. These findings establish PIP as a multifunctional protein important for tissue homeostasis, wound repair, and disease pathogenesis.

Sources cited
1
PIP is a 17-kDa secreted protein with aspartic-type endopeptidase activity that degrades fibronectin and is widely expressed in breast cancer
PMID: 25472539
2
PIP interacts with AQP5 C-terminus to regulate AQP5 trafficking and localization in salivary glands
PMID: 34440877
3
PIP accelerates corneal wound healing by promoting cell migration and exhibiting anti-fibrotic properties
PMID: 36328302
4
PIP expression is regulated by androgen and prolactin through STAT5, Runx2, and CREB1 and is essential for integrin-β1 signaling
PMID: 25472539
5
PIP dysfunction correlates with abnormal AQP5 distribution in Sjögren's syndrome patients
PMID: 34440877
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.34Weak
chronic laryngitisOpen Targets
0.22Weak
diabetic ketoacidosisOpen Targets
0.20Weak
Alzheimer diseaseOpen Targets
0.08Suggestive
sebaceous of Jadassohn nevusOpen Targets
0.07Suggestive
isolated asymptomatic elevation of creatine phosphokinaseOpen Targets
0.06Suggestive
hepatocellular carcinomaOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
breast carcinomaOpen Targets
0.05Suggestive
pentosuriaOpen Targets
0.04Suggestive
breast cancerOpen Targets
0.04Suggestive
infectionOpen Targets
0.04Suggestive
triple-negative breast cancerOpen Targets
0.04Suggestive
Extramammary Paget DiseaseOpen Targets
0.04Suggestive
ovarian neoplasmOpen Targets
0.04Suggestive
inflammatory bowel disease 30Open Targets
0.03Suggestive
chronic intestinal pseudoobstructionOpen Targets
0.03Suggestive
proctitisOpen Targets
0.03Suggestive
immunodeficiency 76Open Targets
0.03Suggestive
platelet abnormalities with eosinophilia and immune-mediated inflammatory diseaseOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
AZGP1Protein interaction100%KRT7Protein interaction85%KRT20Protein interaction84%KELProtein interaction78%APODProtein interaction73%SCGB2A2Protein interaction73%
Tissue Expression6 tissues
Lung
100%
Liver
30%
Ovary
20%
Brain
10%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PIPAZGP1KRT7KRT20KELAPODSCGB2A2
PROTEIN STRUCTURE
Preparing viewer…
PDB3ES6 · 3.23 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.26LoF Tolerant
pLIⓘ
0.31Tolerant
Observed/Expected LoF0.41 [0.16–1.26]
RankingsWhere PIP stands among ~20K protein-coding genes
  • #3,091of 20,598
    Most Researched147 · top quartile
  • #13,277of 17,882
    Most Constrained (LOEUF)1.26
Genes detectedPIP
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PLEKHS1 drives PI3Ks and remodels pathway homeostasis in PTEN-null prostate.
PMID: 37567175
Mol Cell · 2023
1.00
2
Structural mechanisms of PIP
PMID: 40433952
Elife · 2025
0.90
3
Unraveling Human AQP5-PIP Molecular Interaction and Effect on AQP5 Salivary Glands Localization in SS Patients.
PMID: 34440877
Cells · 2021
0.80
4
Phosphatidylinositol 4,5-bisphosphate activation mechanism of human KCNQ5.
PMID: 40172963
Proc Natl Acad Sci U S A · 2025
0.70
5
The membrane electric field regulates the PIP
PMID: 37192161
Proc Natl Acad Sci U S A · 2023
0.60