Pld4, or Phospholipase D4, is an endolysosomal protein involved in multiple biological functions. It is an exonuclease that digests ssDNA and ssRNA, regulating innate immunity [3,4,5,7,8]. It also participates in the synthesis of lysosomal S,S-Bis(monoacylglycero)phosphate (BMP), a crucial lipid for lipid degradation in lysosomes, especially for gangliosides [1,2].

Deletion of Pld4 in murine tissues (such as the spleen where it is highly expressed) markedly reduced BMP levels, leading to gangliosidosis and lysosomal abnormalities, indicating its importance in maintaining normal lipid metabolism [1,2]. Pld4 -deficient mice developed an inflammatory disease, marked by elevated levels of interferon-γ (IFN-γ) and splenomegaly, suggesting its role in regulating the immune response [8]. Pld4 mutant mice also showed autoimmune phenotypes compatible with systemic lupus erythematosus (SLE), including splenomegaly, lymphadenopathy, and autoantibody production [6].

In conclusion, Pld4 is essential for lipid degradation in lysosomes and immune response regulation. Studies using Pld4 knockout and mutant mouse models have revealed its significance in diseases like gangliosidosis, inflammatory diseases, and SLE, providing insights into the underlying mechanisms and potential therapeutic targets.