SACM1L is a phosphoinositide phosphatase that primarily catalyzes the hydrolysis of phosphatidylinositol 4-phosphate (PtdIns(4)P) and shows optimal activity when binding PtdIns(4)P in 'cis' configuration 1234. The enzyme can also hydrolyze phosphatidylinositol 3-phosphate (PtdIns(3)P) and has low activity towards phosphatidylinositol-3,5-bisphosphate. SACM1L functions in cellular membrane regulation and autophagy, where its enzymatic activity is essential for suppressing intracellular bacterial replication by preventing PtdIns(4)P accumulation on bacteria-containing autophagosomes, thereby facilitating proper fusion with lysosomes 5. The enzyme also controls Golgi V-ATPase assembly through regulation of trans-Golgi network membrane composition, maintaining proper cholesterol and PtdIns(4)P balance 6. Disease associations include COVID-19 severity, where SACM1L is identified as a putative causal gene 7, and intervertebral disc degeneration, where it shows elevated expression 8. Additionally, genetic variants in SACM1L are associated with sexual side-effects from bupropion antidepressant therapy 9.