Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Binds to vinculin and to the SH3 domain of SRC. Interacts with GIT1, NUDT16L1/SDOS, PARVA, PARVB, SORBS1 and TGFB1I1. Component of cytoplasmic complexes, which also contain GIT1, ARHGEF6 and PAK1. Binds ASAP2. Interacts with RNF5 and PDCD10 (By similarity). Interacts with NEK3 and this interaction is prolactin-dependent (By similarity). Interacts with PTK2/FAK1 and PTK2B/PYK2 (By similarity). Interacts with PTK6 (By similarity). Interacts with CD36. Interacts (via cytoplasmic domain) with CEACAM1; the interaction is phosphotyrosyl-dependent (By similarity). Interacts with PXN; this complex stabilizes actin dynamics (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 (By similarity). 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.