SAMD12 (sterile alpha motif domain containing 12) is a multifunctional adaptor protein involved in cell signaling pathways and neurological function. The protein serves as a key regulator in cancer cell motility by coupling AXL receptor tyrosine kinase signaling to ARF6 GTPase activation, promoting cell migration and metastasis 1. SAMD12 functions as a master regulator of MAP4K kinases by binding to CNKSR scaffold proteins with high affinity, effectively displacing MAP4K kinases and modulating neuronal synapse development 2. Disease relevance is primarily established through intronic TTTCA and TTTTA repeat expansions in SAMD12, which cause benign adult familial myoclonic epilepsy (BAFME), a neurological disorder characterized by myoclonic tremor and seizures 3. These pathogenic repeat expansions vary in length and configuration, with longer repeats correlating with earlier disease onset and increased severity 4. The shortest pathogenic TTTCA expansion identified contains only 3 repeats, demonstrating that even minimal expansions can be disease-causing 5. Additionally, reduced SAMD12 expression has been implicated in hepatocellular carcinoma progression, where it acts as a tumor suppressor 6. The protein's involvement in both neurological disorders and cancer highlights its critical role in cellular signaling networks.