ATG9A-dependent, LC3-independent autophagy curbs the immune system to protect against disease

Selective autophagy is generally believed to require the conjugation of microtubule associated protein 1 light chain 3 (LC3) proteins (or other autophagy-related 8 [ATG8] family members) on the inner phagophore leaflet to enable the recruitment of cargo-bound selective autophagy receptors. However, this paradigm is challenged by the discovery that cytosolic cargoes can still be selectively targeted by phagophores even in the absence of LC3 proteins. In a recent study published in Immunity, we discovered that ATG9A-dependent, LC3-independent autophagy facilitates the degradation of multiple inflammatory signaling complexes to prevent an inflammatory skin disease.