KRT16 encodes keratin 16, a type I intermediate filament protein that serves as a critical regulator of skin barrier function and innate immunity. KRT16 is upregulated in response to skin injury and stress, where it acts as a barrier alarmin molecule that modulates keratinocyte proliferation, migration, and inflammatory responses 1. The protein plays a key role in regulating innate immune signaling by negatively controlling type I interferon responses through interaction with RIG-I-like receptor pathway effectors, including 14-3-3ε, thereby spatially restricting immune activation in the suprabasal epidermis 2. KRT16 expression serves as a biomarker for epidermal hyperplasia in inflammatory skin conditions including atopic dermatitis and psoriasis 34. Mutations in KRT16 cause pachyonychia congenita, an autosomal dominant disorder characterized by hypertrophic nails and palmoplantar keratoderma 56. The protein's dual role as both a structural cytoskeletal component and immune regulator positions it as a critical mediator of skin homeostasis, with dysregulation contributing to chr17 inflammatory skin diseases through altered keratinocyte behavior and excessive immune activation.