Molecular insights into nagashima-type palmoplantar keratoderma: SERPINB7 mutation spectrum and mechanistic...

Nagashima-type palmoplantar keratoderma (NPPK) is a common inherited palmoplantar keratoderma predominantly affecting East Asian populations and caused by biallelic loss-of-function variants in the SERPINB7 gene. Clinically, NPPK is characterized by diffuse, non-progressive hyperkeratoderma of the palms and soles with erythema extending beyond the palmoplantar margins, frequently accompanied by hyperhidrosis and malodor. Although the disease course is generally benign, these features may lead to a considerable psychosocial burden. Advances in next-generation sequencing have expanded the mutational spectrum of SERPINB7 and clarified founder effects in different populations, while mechanistic studies have highlighted the essential role of SERPINB7 in maintaining epidermal protease-antiprotease balance and barrier homeostasis. These insights have enabled the development of mutation-targeted therapeutic approaches, most notably topical gentamicin-induced readthrough therapy for nonsense mutations. This review summarizes current knowledge and recent advances in the epidemiology, genetics, pathogenesis, clinical features, and management of NPPK, with particular emphasis on emerging precision treatment strategies.