PIKFYVE

PIKFYVE encodes phosphatidylinositol-3-phosphate 5-kinase, a lipid kinase that phosphorylates phosphatidylinositol-3-phosphate to generate phosphatidylinositol-3,5-bisphosphate, regulating endosomal trafficking and vesicle homeostasis. Key aliases include PIP5K3 and FYVE finger-containing phosphoinositide kinase. It modulates mTOR signaling and autophagy through endolysosomal membrane dynamics, with dysfunction linked to neurodegenerative disorders like Charcot-Marie-Tooth disease and cancer via altered cell growth pathways.
Preclinical studies target PIKFYVE with small-molecule inhibitors (e.g., apilimod) to disrupt endosomal-lysosomal function in hematological malignancies and viral infections, leveraging its role in viral replication. Inhibitor development focuses on enhancing specificity for treating lysosomal storage diseases and metastatic cancers, though clinical translation requires addressing off-target effects on normal cellular trafficking.