PIK3C3 encodes a class III phosphatidylinositol 3-kinase that serves as a critical regulator of autophagy and endosomal trafficking. The enzyme functions as the catalytic subunit of the BECN1-PIK3C3 complex, where it generates phosphatidylinositol-3-phosphate (PtdIns3P) on autophagosome and endosomal membranes 12. PIK3C3 is essential for autophagosome formation and maturation, working downstream of AMPK activation and ULK1 complex signaling 1. The kinase activity can be regulated by post-translational modifications, including acetylation, which modulates autophagy initiation 3. PIK3C3 plays crucial roles in selective autophagy pathways, including lipophagy for lipid droplet degradation in liver metabolism and mitophagy for mitochondrial quality control 45. The enzyme is also involved in endometrial tissue homeostasis and cancer progression 6. Dysregulation of PIK3C3-mediated autophagy is implicated in various diseases including fatty liver disease, neurodegenerative disorders, and autoimmune conditions 45. Additionally, PIK3C3 kinase activity is required for SARS-CoV-2 replication, highlighting its role in viral pathogenesis. The enzyme represents an attractive therapeutic target for autophagy modulation in cancer and metabolic diseases 2.