Pareuchiloglanis anteanalis is an endangered endemic species native to the upper Yangtze River. To adapt to fast-flowing highland river environment, the skin structures in its upper jaw and fin-ray regions have undergone specialization, providing strong adhesive capabilities. To elucidate the regulatory basis of this specialization, we examined the histological features of the specialized skin, performed comparative transcriptomic analyses between specialized skin (from the upper jaw and pectoral fin) and non-specialized skin (from the fin-ray region), screened and identified genes associated with skin specialization. The results showed that the specialized epidermis of the upper jaw and pectoral fin develops dense ridges, grooves and sensory bud structures, which enhance adhesion. Tissue-origin mapping showed that these specialized tissues formed adjacent clusters with highly similar gene expression profiles and strong homology. Compared to f the non-specialized skin from the fin-ray region, the upper jaw and pectoral fin shared 251 differentially expressed genes (DEGs), including 146 upregulated and 105 downregulated genes. KEGG enrichment analysis indicated that the significantly enriched pathways were primarily related to cell projection assembly (GO:0030030) and collagen metabolism (KO04310). qRT-PCR validation confirmed that both igs10 and adcy5 were significantly upregulated in the specialized skin (P < 0.05), suggesting their regulatory roles in skin specialization. This study is the first to reveal the histological basis of the specialized skin structure and adhesive function of P. anteanalis, demonstrate the morphological specialization of the epidermal ridge–groove structures and sensory buds, and identify genes associated with skin specialization through comparative transcriptomics. These findings provide a molecular basis for understanding the adaptive regulation of skin specialization in sisorid fishes inhabiting the upper Yangtze River.