MAST3 (microtubule associated serine/threonine kinase 3) is a microtubule-associated serine/threonine kinase that plays critical roles in neuronal function and inflammatory signaling. The protein exhibits kinase activity that phosphorylates target substrates including ARPP-16, a protein phosphatase 2A inhibitor 1. MAST3 functions through complex regulatory mechanisms, including reciprocal regulation with PKA kinase, where PKA phosphorylation inhibits MAST3 activity and creates a cAMP-regulated switch in PP2A inhibition 1. In breast cancer, MAST3 acts as a tumor suppressor by directly interacting with YAP (yes-associated protein), promoting its phosphorylation-mediated ubiquitination and degradation, thereby inhibiting cell proliferation and invasion 2. The gene is strongly associated with neurological diseases, particularly developmental and epileptic encephalopathy, where de novo missense variants in the serine-threonine kinase domain cause seizure disorders with gain-of-function effects 34. MAST3 expression is restricted to excitatory neurons in the cortex during late prenatal and postnatal development 3. Additionally, MAST3 modulates inflammatory responses by regulating NF-κB activity and TLR4 signaling pathways, implicating it in inflammatory bowel disease pathogenesis 56. The protein's dysfunction contributes to various pathological conditions through disrupted cellular signaling and developmental processes.