Ly6a, also known as Stem Cell Ag-1 and T cell-activating protein, is a glycosylphosphatidylinositol (GPI)-anchored protein. It has diverse functions, being involved in hematopoiesis, and may play a role in various biological processes such as cell fate determination, immune response regulation, and blood-brain barrier (BBB) transport. Its associated pathways include those related to T-cell activation and metabolism, and it is of significance in understanding immune-related diseases and gene therapy for neurological diseases [1,4,5,6].

In a Sca-1 (Ly6a) knockout (KO) mouse model, loss of Sca-1 alone had little effect on bladder development or function but reduced the total number of mesenchymal stem cells by 30%. After partial bladder outlet obstruction (PO), bladders from Sca-1-null KO male mice were larger, with more collagen and less muscle, indicating that Ly6a protects the bladder from fibrotic remodeling after obstruction, in part by influencing the proliferation of cells responding to the injury [2]. Also, the expression level of Ly6a is likely the determining factor for differential efficacy of AAV-PHP.B in transducing the central nervous system (CNS) across different mouse strains, and high BBB transport is linked to the binding of AAV-PHP.B with LY6A (SCA-1) [3,4].

In conclusion, Ly6a has essential functions in processes like immune response modulation, cell fate determination during development, and BBB-related gene delivery. Mouse KO models have been crucial in revealing its role in preventing bladder fibrosis and in understanding the mechanism of CNS-targeted gene therapy, contributing to the study of related diseases and potential therapeutic strategies.