Core Viewpoint - The study reveals that lactylation of YTHDC1 at K82 enhances its phase separation, stabilizing oncogenic mRNA and promoting the progression of renal cell carcinoma (RCC) in a hypoxic environment [2][6][9]. Group 1: Research Findings - The research systematically mapped the lactylation profile of proteins under hypoxic conditions in RCC, focusing on the functional mechanism of YTHDC1 K82 lactylation [2][6]. - Elevated levels of global lysine lactylation (Kla) were found in human RCC tissues and cells, which promotes malignant development of RCC [6][7]. - YTHDC1 K82 lactylation, mediated by p300 under hypoxic conditions, promotes the malignancy of RCC both in vitro and in vivo [6][7]. Group 2: Mechanism of Action - YTHDC1 K82 lactylation enhances the phase separation of YTHDC1, leading to the expansion of nuclear condensates that protect oncogenic transcripts BCL2 and E2F2 from degradation by the PAXT-EXO complex [6][7][9]. - The study highlights that the increased lysine lactylation regulates the stability of YTHDC1 target genes, thereby facilitating the progression of RCC [9]. Group 3: Study Highlights - Quantitative lactylation proteomics analysis revealed high levels of lactylation modification proteins under hypoxic conditions [7]. - The study identifies a novel regulatory pathway involving YTHDC1 lactylation that opens new therapeutic targets in the intersection of tumor metabolism and RNA regulation [2][6].