In this study, we uncovered a multifaceted role for STK38 in papillary renal cell carcinoma (pRCC), delineating its dual contributions to Hedgehog (Hh) pathway activation and tumor-associated chromatin release, ultimately linking it to the maintenance of stem-like tumor cell populations and tumor heterogeneity. The gene discussed is STK38; the disease is papillary renal cell carcinoma.