RUSC1, also known as NESCA, shares with the related protein RUSC2 a common domain structure of RUN, leucine zipper and SH3 domain in addition to over 30% amino acid identity. RUSC1 is an adapter protein that can bind to the TrkA receptor and is necessary in the NGF-induced neurite growth of PC12 cells. RUSC1 has also been shown to interact with IκB kinase- (IKK-) gamma, the regulatory subunit of the IKK complex that is required for NF-κB activation in many signaling pathways such as TNF-R or the TLR pathways. RUSC1 can also bind to the E3 ubiquitin ligase TRAF6, which then catalyzes RUSC1 polyubiquitination. Since overexpression of RUSC1 strongly inhibits TRAF6-mediated polyubiquitination of IKK-gamma, RUSC1 may be a link in the IKK-gamma-mediated NF-κB activation pathway.