WIPI2 (WD repeat domain, phosphoinositide interacting 2) is a critical autophagy regulator that recruits the ATG12-ATG5-ATG16L1 complex to omegasomes and preautophagosomal structures, initiating ATG8 lipidation and autophagosome formation 1. The protein binds phosphatidylinositol-3-phosphate (PI3P) and functions in starvation-induced autophagy and selective autophagy of pathogenic bacteria, including Salmonella 1. WIPI2 serves as a key component in the cGAS-STING innate immune pathway, where it directly interacts with STING to enable LC3 lipidation independent of canonical VPS34-beclin complexes, facilitating cytoplasmic DNA and viral clearance 23. During mitosis, WIPI2 is polyubiquitinated and degraded via CRL4 ubiquitin ligases, suppressing autophagy during cell division 1. WIPI2 is also recruited to endoplasmic reticulum subdomains by VAPs (VAMP-associated proteins) to facilitate reticulophagy, the selective autophagy of impaired ER regions 4. Disease associations include Crohn's disease, age-related macular degeneration, hepatocellular carcinoma, and colorectal cancer, reflecting autophagy's role in cellular homeostasis and immune function. WIPI2 represents a therapeutic target for autophagy-related disorders and conditions benefiting from enhanced selective autophagy.