Numb-associated kinases: physiological functions and roles in viral infection

Numb-associated kinases (NAKs) are a family of evolutionarily conserved serine/threonine kinases, encompassing adaptor-associated kinase 1 (AAK1), cyclin G-associated kinase (GAK), bone morphogenetic protein 2-inducible kinase (BMP2K), and serine/threonine kinase 16 (STK16). NAKs are widely involved in various physiological processes, such as endocytosis, intracellular transport, cell differentiation, autophagy, and signal transduction. In recent years, studies have shown that NAKs play a key role in different life cycle stages including virus entry, assembly, release, and immune escape of various viruses. Furthermore, small-molecule inhibitors targeting NAKs have been applied in clinical research and treatment of related physiological or viral infectious diseases. This article systematically reviews the primary physiological functions of NAKs and their roles in viral infection, aiming to provide a theoretical foundation for elucidating the pathogenic mechanisms of viruses and developing novel therapeutic drugs targeting NAKs.