Unc-51-like autophagy activating kinase 1 (ULK1) and Unc-51-like autophagy activating kinase 2 (ULK2) (ULK1 (for Unc-51-like autophagy activating kinase 1), ULK2 (for Unc-51-like autophagy activating kinase 2))

ULK kinase-1 and ULK kinase-2 are serine/threonine protein kinases that initiate autophagy by phosphorylating and organizing autophagy-specific regulatory complexes[1]. ULK1, together with FIP200, ATG13, and ATG101, forms the core autophagy induction machinery in mammalian cells, coordinating upstream (nutrient sensing via mTORC1) and downstream molecular events critical for the formation and expansion of autophagosomes. ULK2 is structurally similar (~78% kinase domain identity), yet exhibits unique interaction motifs and regulatory roles, indicating partially overlapping but also distinct biological functions—ULK1 is more involved in apoptosis and intracellular transport, while ULK2 regulates homeostasis and cytokine responses[1][2][4]. Both kinases are increasingly targeted in diseases where autophagy plays a pathogenic role, and inhibitors modulating their catalytic activity are in development for cancer and inflammation[3][4][2].

Other names

ULK1ULK2Unc-51-like kinase 1Unc-51-like kinase 2Autophagy-related protein 1 homolog (ATG1 homolog)Autophagy initiator kinases

Inhibition of kinase activity (ATP-competitive inhibition blocks autophagy initiation); Conformational modulation of kinase domain; Potential dual inhibition (both ULK1 and ULK2) for robust autophagy blockade