CD49f protein, also known as integrin-6 (ITGA6) or integrin alpha-6 chain protein, is a type I transmembrane glycoprotein belonging to the α-subfamily. CD49f may have two distinct cytoplasmic domains resulting from alternative splicing variants of mRNA, α6A and α6B, which exhibit different stem-like functions. Among them, the α6B variant is closely related to the cancer stem cell (CSC) phenotype. CD49f plays a crucial role in cell adhesion to the extracellular matrix. It typically forms heterodimers with integrin β1 and β4, serving as a receptor for various laminin proteins. Research has shown that the heterodimerization of CD49f interacts with signaling pathways, inducing stem-like and invasive characteristics in breast cancer cells. Moreover, CD49f is not only a stemness-related gene that can serve as a surface marker for various stem cells, such as embryonic stem cells, neural stem cells, and hematopoietic stem cells, but also plays a significant role in maintaining stem cell self-renewal and stemness through its interaction with ECM components (e.g., laminin) in the microenvironment. Previous studies have also found that the adhesion molecule CD49f is differentially expressed in fetal and adult bone marrow-derived mesenchymal stem cells (BMSCs), and the interaction between stem cells and their supporting cells or ECM in the microenvironment mediated by CD49f is crucial for maintaining stemness.