Phosphoinositide kinase, FYVE finger containing (PIKfyve) (PIKfyve)

Phosphoinositide kinase, FYVE finger containing (PIKfyve) is a large, evolutionarily conserved lipid kinase that plays a central role in endosomal membrane homeostasis (UniProt Q9Y2I7). It is primarily responsible for synthesizing phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] from phosphatidylinositol 3-phosphate [PI(3)P], a reaction critical for the maturation and trafficking of endosomes and lysosomes (PubMed: 28249986). Beyond membrane trafficking, PIKfyve is involved in diverse cellular processes including autophagy, cytokinesis, and the regulation of ion channels and glucose transporters (NCBI Gene ID: 200576). Dysregulation of PIKfyve is associated with several pathologies, including neurodegenerative diseases like ALS and Charcot-Marie-Tooth disease, as well as various cancers where it supports nutrient scavenging (PubMed: 33009271). In the context of infectious diseases, PIKfyve has emerged as a key host factor for the entry and egress of several viruses, including SARS-CoV-2 and Ebola (PubMed: 32555382). Pharmacological inhibition of PIKfyve by small molecules such as apilimod leads to the accumulation of enlarged endosomal vacuoles, which can disrupt viral replication and induce cell death in certain cancer types (PubMed: 32555382).

Other names

PIP5K3FAB1CFDFYVE finger-containing phosphoinositide kinase1-phosphatidylinositol 3-phosphate 5-kinasePhosphatidylinositol 3-phosphate 5-kinase

Inhibition of the kinase activity of PIKfyve, which prevents the phosphorylation of phosphatidylinositol 3-phosphate (PI3P) to phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), thereby disrupting endosomal maturation and trafficking (PubMed: 32555382).