EXPH5, also known as Slac2-b, encodes exophilin-5, a protein involved in intracellular vesicle transport [3,4]. It is associated with the exosome secretion pathway, where it has been shown to play a role in this process. In particular, it is related to the functions of Rab27a and Rab27b, which control different steps of the exosome secretion pathway. Silencing EXPH5 inhibits exosome secretion, indicating its importance in this cellular mechanism [2].

Mutations in EXPH5 have been found to underlie a rare subtype of autosomal recessive epidermolysis bullosa simplex (EBS) [3,5]. 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]. Different mutations in EXPH5, such as compound heterozygosity for c.1947dupC and c.2249C > A, or a novel homozygous deletion, result in a skin fragility phenotype with minimal blistering compared to other forms of basal EBS [3,6]. Additionally, EXPH5 has been identified as a potential diagnostic gene biomarker of the late stage of chronic obstructive pulmonary disease (COPD). In the late stage of COPD, especially in main lung cell types AT1 and AT2, EXPH5 genes are significantly downregulated. It also shows correlations with certain immune cells, having a positive correlation with NK cells resting, mast cell resting, eosinophils, and a negative correlation with T cell gamma delta, macrophages M1 [1].

In conclusion, EXPH5 is crucial for intracellular vesicle transport and exosome secretion. Its mutations are linked to a rare form of EBS, causing skin fragility. In addition, its down-regulation in the late stage of COPD and correlations with immune cells suggest its importance in both skin-related and respiratory diseases. The study of EXPH5 through these disease-associated findings helps to understand its biological functions and provides potential diagnostic and therapeutic implications.