C1orf35 (Chromosome 1 open reading frame 35) is an oncogenic regulator implicated in multiple cancer types through distinct but convergent mechanisms. In multiple myeloma, C1orf35 promotes tumorigenesis by activating c-MYC transcription through binding to the i-motif element in the c-MYC promoter 1. This c-MYC activation drives cell cycle progression from G1 to S phase and correlates with disease progression 1. C1orf35 expression also negatively correlates with overall survival in myeloma patients 2. Mechanistically, C1orf35 enhances cellular metabolism by simultaneously promoting both aerobic glycolysis via the c-MYC/PKM2 pathway and oxidative phosphorylation through interaction with LRPPRC 2. In colorectal cancer, C1orf35 functions as a dual-activity oncoprotein: it drives tumor-intrinsic proliferation and migration through c-Myc-mediated upregulation of proline biosynthesis enzyme PYCR2, while also suppressing anti-tumor CD8+ T-cell infiltration in a non-cell-autonomous manner 3. Elevated C1orf35 expression correlates with advanced tumor stage and reduced overall survival in CRC 3. Genome-wide association studies identified a missense variant in C1orf35 (rs145743393) as significantly associated with preeclampsia in multiplex families, though this finding required replication 4. C1orf35 emerges as a multi-faceted therapeutic target across hematologic and solid malignancies.