OCT1 is known to regulate normal cell and CSC function.33 Loss of OCT1 in the colon was associated with restricted tumorigenicity.43 High OCT1 protein levels are correlated with the frequency of CD24 (low)/CD44 (high) cancer-initiating cells in primary malignant tissue.33 OCT1 is a transcription factor for ALDHs.27 Importantly, we show that CSN6 can reduce TRIM21-mediated OCT1 ubiquitination to regulate ALDH1A1 mRNA expression, thereby establishing the CSN6–TRIM21–OCT1–ALDH1A1 stemness-promoting axis. Here, COPS6 is linked to cancer.