Krt32, a member of the keratin gene family, is predominantly localized in basal keratinocytes. It plays a crucial role in regulating skin immune homeostasis by antagonizing the NF-κB pathway. Mechanistically, it binds to NEMO, promoting its excessive K48-linked polyubiquitination and degradation, thus hindering IKK complex formation [1].

In a case-control study, heterozygous mutations in Krt32 were significantly associated with pityriasis rubra pilaris (PRP) in the Han Chinese population. Krt32 knockout mice exhibited a PRP-like dermatitis phenotype, suggesting that loss-of-function mutations in Krt32 among PRP patients lead to NF-κB hyperactivation and compromise the anti-inflammatory function of keratinocytes in response to external pro-inflammatory stimuli [1].

In conclusion, Krt32 is essential for maintaining skin immune homeostasis through its regulation of the NF-κB pathway. The study of Krt32 knockout mice has provided valuable insights into the role of Krt32 in the development of PRP, highlighting its potential as a therapeutic target for this inflammatory skin disease [1].

References:

1. Shi, Peidian, Chen, Wenjie, Lyu, Xinxing, Liu, Hong, Zhang, Furen. 2024. Loss-of-function mutations in Keratin 32 gene disrupt skin immune homeostasis in pityriasis rubra pilaris. In Nature communications, 15, 6259. doi:10.1038/s41467-024-50481-z. https://pubmed.ncbi.nlm.nih.gov/39048559/