MAP4K3 is a serine/threonine kinase that serves as a critical regulator of multiple cellular signaling pathways and disease processes 1. The protein functions as an upstream activator of JNK signaling under environmental stress and inflammatory conditions, while also playing important roles in T-cell activation and immune responses 12. MAP4K3 directly interacts with and phosphorylates PKCθ at Ser-538, leading to IKK/NF-κB pathway activation in T cells 1. In autoimmune diseases, MAP4K3 overexpression promotes IL-17A transcription by inducing the AhR-RORγt complex, and elevated MAP4K3 levels correlate with disease severity in systemic lupus erythematosus patients 21. The kinase also regulates autophagy through amino acid-dependent phosphorylation of transcription factor TFEB, retaining it in the cytoplasm and inhibiting autophagy activation 31. In cancer contexts, MAP4K3 promotes metastasis by phosphorylating IQGAP1 and activating Cdc42-mediated cell migration, with overexpression correlating with cancer recurrence in lung and liver cancers 1. Additionally, MAP4K3 can phosphorylate ACE2 protein, stabilizing it by decreasing ubiquitination 4. These diverse functions establish MAP4K3 as a potential therapeutic target for autoimmune diseases, cancer, and aging-related conditions 1.