E3 ubiquitin-protein ligase TRIM9 (TRIM9)

E3 ubiquitin-protein ligase TRIM9 (TRIM9) is a member of the tripartite motif (TRIM) family of proteins, characterized by a RING finger, B-box domains, and a coiled-coil region[1][4]. TRIM9 is a brain-enriched E3 ubiquitin ligase predominantly expressed in cortical neurons where it regulates neuronal development, synaptic function, and cytoskeletal dynamics[2][3][5][7]. It participates in axon guidance, branching, and synaptogenesis, in part by interacting with key synaptic proteins including the netrin-1 receptor DCC and SNAP25, and by modulating exocytosis and actin architecture during neuronal maturation[5][7]. TRIM9 also acts as a regulator of inflammatory and antiviral signaling pathways, negatively controlling NF-κB activation and promoting type I interferon responses through its short isoform, TRIM9s[3]. It is implicated in disease contexts such as glioblastoma (tumor suppression), neurodevelopmental disorders, and inflammatory processes but presently has no drugs that directly target it. Loss of TRIM9 produces neurodevelopmental and synaptic abnormalities in animal models[5][7].

Other names

Tripartite motif-containing protein 9RNF91SPRINGKIAA0282RING finger protein 91RING-type E3 ubiquitin transferase TRIM9SNAP-25-interacting RING finger proteinHomolog of rat RING finger Spring

No specific mechanisms of clinically approved drugs are described for TRIM9; experimental modulation is focused on genetic or molecular interactions.