EXPH5, also known as Slac2-b, encodes exophilin-5, a protein involved in intracellular vesicle transport. It is associated with the exosome secretion pathway as silencing of EXPH5 inhibits exosome secretion, strengthening the link between multivesicular endosomes (MVEs) and exosomes [2].

Mutations in EXPH5 result in autosomal recessive inherited skin fragility, specifically a form of epidermolysis bullosa simplex (EBS) [3]. Transmission electron microscopy of patient skin with EXPH5 mutations shows disruption of keratinocytes in the lower epidermis, cytolysis, acantholysis, keratin filament clumping, and prominent perinuclear cytoplasmic vesicles [3]. Additionally, EXPH5 has been identified as a potential diagnostic gene biomarker for the late stage of chronic obstructive pulmonary disease (COPD). Its expression is significantly downregulated in the late stage of COPD, especially in main lung cell types AT1 and AT2, and it has correlations with certain immune cells such as positive with NK cells resting, mast cell resting, eosinophils, and negative with T cell gamma delta, macrophages M1 [1].

In conclusion, EXPH5 is crucial for intracellular vesicle transport and exosome secretion. Its mutations lead to skin-related disorders like EBS, and its differential expression in COPD may serve as a diagnostic biomarker. The study of EXPH5 in these contexts provides insights into disease mechanisms and potential diagnostic strategies for EBS and COPD.

References:

1. Yang, Yuwei, Cao, Yan, Han, Xiaobo, Xiao, Li, Xie, Lixin. 2023. Revealing EXPH5 as a potential diagnostic gene biomarker of the late stage of COPD based on machine learning analysis. In Computers in biology and medicine, 154, 106621. doi:10.1016/j.compbiomed.2023.106621. https://pubmed.ncbi.nlm.nih.gov/36746116/

2. Ostrowski, Matias, Carmo, Nuno B, Krumeich, Sophie, Moita, Luis F, Thery, Clotilde. 2009. Rab27a and Rab27b control different steps of the exosome secretion pathway. In Nature cell biology, 12, 19-30; sup pp 1-13. doi:10.1038/ncb2000. https://pubmed.ncbi.nlm.nih.gov/19966785/

3. Liu, L, Mellerio, J E, Martinez, A E, Parsons, M, McGrath, J A. . Mutations in EXPH5 result in autosomal recessive inherited skin fragility. In The British journal of dermatology, 170, 196-9. doi:10.1111/bjd.12723. https://pubmed.ncbi.nlm.nih.gov/24443915/