Inositol polyphosphate 5-phosphatase OCRL

OCRL (inositol polyphosphate 5-phosphatase) is a 901-amino acid phosphatase that catalyzes hydrolysis of the 5-position phosphate on phosphatidylinositol 4,5-bisphosphate and related inositol phosphates. The enzyme regulates endosomal trafficking, primary cilia assembly, and phagocytosis through modulation of phosphoinositide signaling (UniProt: Q01968).

OCRL is primarily associated with X-linked monogenic disorders. Loss-of-function mutations cause Lowe oculocerebrorenal syndrome (MIM 309000), characterized by ocular, neurological, and renal defects, and Dent disease 2 (MIM 300555), an X-linked renal tubular disorder with hypercalciuria and progressive renal insufficiency (UniProt: Q01968).

In Alzheimer's disease, OCRL is significantly downregulated in post-mortem human AD brain tissue compared to age-matched controls (mean log2FC: −1.58, Chaparral AD proteomics). This reduction was detected across the subcellular fractions examined in TMT-labeled quantitative proteomics analysis. The functional significance of OCRL downregulation in AD pathology remains to be determined.