Lymphocyte antigen 6 complex locus A (Ly6A)

Lymphocyte antigen 6 complex locus A, widely known as Sca-1, is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein that serves as a definitive marker for hematopoietic stem cells in mice (UniProt P05533). It belongs to the Ly6/uPAR family and plays a pivotal role in regulating T-cell activation, cell adhesion, and the self-renewal of various progenitor cells (Holmes & Stanford, 2007). In the field of biotechnology, Ly6A has gained prominence as the primary receptor used by engineered adeno-associated virus (AAV) capsids, such as AAV-PHP.B, to cross the blood-brain barrier, making it a central focus for central nervous system drug delivery research (Houtman et al., 2019). While it is highly expressed in murine vascular endothelium and immune cells, the absence of a direct human ortholog remains a significant hurdle for translating Ly6A-targeted therapies to the clinic. Nevertheless, it remains an essential target for understanding stem cell biology and developing next-generation gene therapy vectors (Huang et al., 2019).

Other names

Sca-1Stem cell antigen-1Ly-6A.2Ly-6E.1T-cell activating proteinTAP

Acts as a docking receptor for engineered viral capsids to facilitate transport across the blood-brain barrier via transcytosis and modulates T-cell receptor (TCR) signaling through association with Fyn and Lck kinases (Huang et al., 2019; UniProt P05533).