CD53 is a tetraspanin protein exclusively expressed in immune cells that functions as a structural component of tetraspanin-enriched microdomains (TEMs), serving as a platform for receptor clustering and cell signaling 1. It plays critical roles in B-cell and T-cell development and activation by promoting BCR signaling through PKC recruitment to the plasma membrane and stabilizing L-selectin expression for lymph node homing 2. CD53 participates in diverse immune processes including cell adhesion, migration, and protein trafficking 1. Beyond lymphocytes, CD53 is expressed on dendritic cells, macrophages, and natural killer cells, supporting their inflammatory and immune functions 1. In disease contexts, CD53 emerges as a key hub gene in lupus nephritis with high diagnostic accuracy (AUC=0.995), correlating with immune cell infiltration and disease severity 3. Single-cell analyses identify CD53+ megakaryocytes as specialized immune-responsive cells capable of bacterial clearance and antigen presentation 4. CD53 is also associated with macrophage polarization in liver cancer and serves as a marker of immune activation during HBV disease progression 56. Patients lacking functional CD53 experience recurrent infections, indicating an essential, non-redundant role in immune homeostasis 1.