RUSC1 is a cytoplasmic adapter protein containing RUN, leucine zipper, and SH3 domains that functions in multiple cellular signaling pathways. At the molecular level, RUSC1 associates with the adapter-like complex 4 (AP-4) at the trans-Golgi network and regulates neurotrophin signaling during neuronal development 1. The protein translocates to the nuclear envelope in response to nerve growth factor stimulation and facilitates NGF-dependent neurite outgrowth in a RUN domain-dependent manner 1. RUSC1 also regulates polyubiquitination of IKBKG and participates in NF-κB pathway signaling. Dysregulation of RUSC1-AS1, a long noncoding RNA transcribed from the RUSC1 locus, is implicated in cancer progression. In breast cancer, RUSC1-AS1 is upregulated and promotes cell viability and metastasis through Wnt/β-catenin signaling 2. Similarly, RUSC1-AS1 is elevated in hepatocellular carcinoma and osteosarcoma, where it functions as a competing endogenous RNA that sequesters microRNAs to activate oncogenic pathways including NOTCH signaling 3 and PI3K/AKT signaling 4. In type 2 diabetes, RUSC1-AS1 is downregulated in inflammatory cell models 5. These studies suggest that RUSC1-AS1 manipulation represents a potential therapeutic target in cancer, though current clinical applications remain investigational.