NUCKS1 (nuclear casein kinase and cyclin-dependent kinase substrate 1) is a highly conserved 27 kDa chr1-associated protein with multiple cellular functions. Primarily, NUCKS1 promotes homologous recombination-mediated DNA repair by binding double-stranded DNA and secondary DNA structures, though with less affinity than RAD51AP1 1. Beyond DNA repair, NUCKS1 functions as a transcriptional regulator involved in chr1 remodeling and gene expression control 2. Mechanistically, NUCKS1 contains consensus phosphorylation sites for casein kinase II and cyclin-dependent kinases, and shares structural similarity with high mobility group proteins 2. In aging contexts, SIRT7-mediated loss promotes NUCKS1 acetylation and chr1 recruitment, activating inflammatory and metabolic genes through interaction with RELA and CEBPβ transcription factors 3. In cancer cells, NUCKS1 promotes tumorigenesis through distinct pathways: osteosarcoma progression via asparagine synthesis elevation 4, and colorectal cancer metastasis by stabilizing HDAC2 and activating AKT signaling 5. Clinically, NUCKS1 demonstrates significant disease relevance. Genetic variants (rs823093) associate with Parkinson's disease susceptibility through enhancer-mediated activation at the PARK16 locus 6 7. Mendelian randomization studies identify NUCKS1 as a causal gene for sarcopenia, where enhanced expression promotes muscle mass and function 8. Elevated NUCKS1 expression correlates with poor prognosis in multiple cancers and serves as a potential therapeutic target.