TRIM21 could catalyze the K63-linked polyubiquitination on programmed cell death-1 (PD-1) at K233, resulting in stabilization of PD-1 by antagonizing its K48-linked polyubiquitination and degradation to impair anti-tumor immunity of CD8+T cells (Shi et al., 2025). The gene discussed is TRIM21; the disease is neoplasm.