BLOC1S1, also known as GCN5L1 and BLOS1, is a small intracellular protein involved in multiple key biological processes. It is a common component of BLOC and BORC multiprotein complexes, playing important roles in endosome and lysosome biology, protein lysine acetylation, energy metabolism, and cellular immune pathways [3,6].

In liver-specific knockout (LKO) mouse hepatocytes, genetic depletion of BLOC1S1 led to autolysosome accumulation due to blunted lysosomal tubulation, disrupting autophagic lysosome reformation (ALR) [1]. BLOC1S1 interacts with the ARL8B-KIF5B complex and WHAMM, which are crucial for lysosomal tubulation. In CD4+ T-cell-specific BLOC1S1 knockout mice, depletion of BLOC1S1 disrupted mitochondrial integrity, leading to activation of cGAS-STING and NF-κB pathways, TH2 polarization, and increased susceptibility to allergic conditions [4,5]. In hepatocyte-specific LKO mice, BLOC1S1 depletion was associated with diminished hepatocyte lipid stores, increased lysosomal content, lipid uptake, and lipolysis [2].

In conclusion, BLOC1S1 is essential for maintaining the homeostasis and function of vacuolar organelles such as mitochondria and endolysosomes. Studies using BLOC1S1 knockout mouse models have revealed its role in processes like ALR, lipid metabolism, and immune regulation, suggesting its potential significance in diseases related to lysosomal dysfunction, lipid metabolism disorders, and immune-related conditions.