ZKSCAN1 is a zinc finger transcription factor with dual roles as both a linear mRNA and circular RNA (circZKSCAN1), functioning as a tumor suppressor across multiple cancer types through distinct mechanisms. As linear mRNA, ZKSCAN1 primarily regulates cellular metabolism 1. The circular form, circZKSCAN1, functions as a competing endogenous RNA (ceRNA) that sponges microRNAs to modulate cancer-related signaling pathways 1. In hepatocellular carcinoma (HCC), circZKSCAN1 encodes a secretory peptide (circZKSaa) that suppresses tumor progression by promoting mTOR ubiquitination via FBXW7, thereby inhibiting the PI3K/AKT/mTOR pathway and sensitizing cells to sorafenib 2. In bladder cancer, circ-ZKSCAN1 acts as a miR-1178-3p sponge to upregulate p21 expression, suppressing proliferation and invasion 3. Conversely, in lung adenocarcinoma, circ-ZKSCAN1 promotes chemotherapy resistance by sponging miR-185-5p to upregulate TAGLN2 4. Clinically, low ZKSCAN1 expression correlates with poor prognosis in HCC and bladder cancer, with circZKSCAN1 levels predictive of recurrence, vascular invasion, and tumor grade 135. Additionally, ZKSCAN1 represents a noncanonical tumor-associated antigen with therapeutic immunotherapy potential 6.