WIPI1 is a scaffold protein of the autophagy machinery that binds phosphatidylinositol 3-phosphate (PtdIns3P) and related lipids at the endoplasmic reticulum to facilitate autophagosome assembly. It functions downstream of ULK1 and PI3-kinase signaling, assisting WIPI2 in recruiting the ATG12–ATG5–ATG16L1 complex, which drives elongation of the nascent autophagosomal membrane. WIPI1 also promotes lipid transfer by ATG2 and participates in selective autophagy pathways including mitophagy and xenophagy of *Staphylococcus aureus*. Beyond canonical autophagy, WIPI1 controls melanosome maturation through MTOR inhibition and regulates endosomal cargo exit through distinct phosphoinositide-binding mechanisms 1. WIPI1 dysregulation is implicated in multiple diseases. In type 2 diabetes, WIPI1 was identified as a hub autophagy-related gene associated with pancreatic β-cell dysfunction 2, and genetic signals colocalize WIPI1 with altered fasting proinsulin levels 3. In septic acute lung injury, WIPI1 downregulation attenuates disease severity through autophagy activation 4. WIPI1 upregulation correlates with right ventricular failure and non-canonical autophagy in heart failure; WIPI1 silencing reduces aldosterone-induced mitochondrial oxidative stress in cardiac myocytes 5. The ABL-ERK-MYC signaling axis represses WIPI1 transcription; enhanced WIPI1 expression promotes autophagosome formation and extends lifespan 6. These findings position WIPI1 as a central regulator of autophagy relevant to metabolic, inflammatory, and cardiac pathologies.