[5] This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to Z-discs.

[8] Skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments.

Alpha-actinin 2 has been shown to interact with KCNA5,[10][11] DLG1,[10] DISC1,[12] MYOZ1,[13] GRIN2B,[14] ADAM12, [15] ACTN3,[16] MYPN,[17] PDLIM3,[18] PKN,[19] MYOT,[20] TTN,[21] NMDAR,[22] SYNPO2,[23] LDB3,[24] and FATZ.

[25][26] It is clear from studies by Hampton et al. that this crosslinking can assume a variety of conformations, with preferences for 60° and 120° angles.

[27] Alpha-actinin-2 also functions in docking signalling molecules at Z-discs, and additional studies have also implicated alpha-actinin-2 in the binding of cardiac ion channels, Kv1.5 in particular.