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Gerronema lapidescens (Lei Wan), a valued medicinal basidiomycete traditionally employed for antiparasitic and digestive ailments, faces severe conservation threats due to unsustainable wild harvesting and the absence of reliable cultivation protocols. To address this crisis and unlock its pharmacotherapeutic potential, we present the first chromosome-scale genome assembly and comprehensive methylome profile for the wild strain G. lapidescens QL01, domesticated from the Qinling Mountains. A multi-platform sequencing strategy (Illumina and PacBio HiFi) yielded a high-quality 82.23 Mb assembly anchored to 11 chromosomes, exhibiting high completeness (98.4% BUSCO) and 46.03% GC content. Annotation predicted 15,847 protein-coding genes, with 81.12% functionally assigned. Genome-wide analysis identified 8.46 million high-confidence single-nucleotide polymorphisms (SNPs). Notably, methylation profiling revealed 3.25 million methylation events, with elevated densities on chromosomes 4, 9, and 10, suggesting roles in gene silencing and environmental adaptation. Phylogenomic analyses clarified the evolutionary status of G. lapidescens, whilst gene family evolution indicated moderate dynamics reflecting niche adaptation. Carbohydrate-Active enzymes (CAZymes) analysis identified 521 enzymes, including 211 Glycoside Hydrolases (GHs), consistent with organic matter degradation. Additionally, 3279 SSRs were catalogued as molecular markers. This foundational resource elucidates G. lapidescens’s genetic architecture, epigenetic regulation, evolutionary history, and enzymatic toolkit, underpinning future research into medicinal compound biosynthesis, environmental adaptation, germplasm conservation, and sustainable cultivation. Full article