Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Interacts in vitro with VCL/vinculin as well as to the SH3 domain of SRC and, when tyrosine phosphorylated, to the SH2 domain of CRK (By similarity). Interacts with GIT1 (By similarity). Interacts with NUDT16L1/SDOS (PubMed:11805099). Interacts with PTK2/FAK1 (PubMed:11799401). Interacts with PTK2B/PYK2 (PubMed:8940124). Interacts with ASAP2 (By similarity). Interacts with unphosphorylated ITGA4 (By similarity). Interacts with RNF5 (By similarity). Interacts with PDCD10 (By similarity). Interacts with NEK3, the interaction is prolactin-dependent (By similarity). Interacts with PTK6 (By similarity). Interacts with TGFB1I1 (By similarity). Interacts with SORBS1 (By similarity). Interacts with PARVB (By similarity). Interacts (via LD motif 4) with PARVA/PARVIN (PubMed:11134073). Interacts (via LD motif 4) with ILK (By similarity). Interacts (via cytoplasmic domain) with CEACAM1; the interaction is phosphotyrosyl-dependent (By similarity). Interacts with LIMA1; this complex stabilizes actin dynamics (By similarity). Interacts with CD36 (via C-terminus) (By similarity). Colocalizes with integrins at the cell periphery. Colocalizes with PXN to membrane ruffles and the leading edge of migrating cells (By similarity). Phosphorylated by MAPK1/ERK2. Phosphorylated on tyrosine residues during integrin-mediated cell adhesion, embryonic development, fibroblast transformation and following stimulation of cells by mitogens. Phosphorylation at Ser-244 by CDK5 reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation (By similarity). Phosphorylation at Tyr-31 and Tyr-118 by PTK6 promote the activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion (By similarity). Phosphorylation at Ser-250 by SLK is required for PXN redistribution and cell motility (By similarity). Belongs to the paxillin family.