MAP3K7 (mitogen-activated protein kinase kinase kinase 7) is a serine/threonine kinase that serves as a critical hub in inflammatory and stress-response signaling pathways. Structurally, MAP3K7 functions as an upstream activator of multiple MAPK cascades, phosphorylating MAP2K3/MKK3, MAP2K6/MKK6, and MAP2K7/MKK7 to activate p38 MAPK and JNK pathways, ultimately controlling transcription factor AP-1 12. Beyond MAPK signaling, MAP3K7 serves as a key activator of NF-κB by phosphorylating IKBKB/IKKB within the IKK complex, with recruitment to polyubiquitin chains occurring through TAB2 and TAB3 adaptor proteins 32. MAP3K7 mediates signal transduction downstream of TRAF6, IL-1, TGF-β, TLRs, and BCR 45. Recently, MAP3K7 was shown to phosphorylate SQSTM1/p62 during metabolic stress, creating a feedback loop that activates both AMPK and NRF2 for enhanced antioxidant defense 6. Clinically, MAP3K7 mutations cause two distinct genetic disorders: loss-of-function mutations cause cardiospondylocarpofacial syndrome with cardiac manifestations, while other mutations cause frontometaphyseal dysplasia 7. MAP3K7 variants are associated with dilated cardiomyopathy susceptibility in genome-wide association studies 8, and MAP3K7 expression increases in kidney intercalated cells following uropathogenic E. coli exposure, suggesting roles in innate immune defense 9.