i/ Cytoskeletal organization and cell motility. Ability of α-actinin 4 to crosslink actin stress fibers and binding of transmembrane proteins in the cell junctions contributes to the maintenance of cell shape and anchoring to the adjacent extracellular matrix. α-Actinin 4 is involved in targeting JRAB/MICAL-L2 complex (important for recycling of occludin) to plasma membrane of TJs and participates in TJ formation (Nakatsuji et al., 2008).
Together with α-actinin 1, α-actinin 4 is essential for the formation of dorsal stress fibers in the migrating cells, composition and maturation of focal adhesions. Tyrosine phosphorylation of α-actinins is critical in those processes. In the absence of α-actinins focal adhesions have reduced affinity to extracellular matrix proteins (Feng et al., 2013).
Expression of α-actinin 4 is upregulated in the migrating cells and localized in their protrusions (Honda et al., 1998). In the stepwise process of cell movement it is believed that α-actinin 4 (most probably both non-muscle isoforms) is important for the detachment of rear cell end through organized disassembly of focal adhesions by calpain (Bhatt et al., 2002; Shao et al., 2013). Complementary mechanism promoting focal adhesions disassembly is binding of PIP3, a lipid product of phoshoinositide 3-kinase, to the α-actinins CH2 domain. That interaction reduces affinity of α-actinins to actin and integrin (Greenwood et al., 2000).

ii/ Modulation of gene transcription. It has been shown that α-actinin 4 interacts with nuclear receptors (estrogen receptor α in MCF-7 cells, vitamin D receptor in CV-1 cells, retinoic acid receptor and peroxisome proliferator-activated receptor γ in podocytes) and transcriptional co-activators (PCAF, SRC-1) through its LXXLL motif (Khurana et al., 2012a; Khurana et al., 2012b). Binding affinity to the nuclear factors was stronger in the alternatively spliced (short) isoform identified in a human cDNA library during earlier study (Chakraborty et al., 2006). All the above interactions enhance gene transcription. In addition, α-actinin 4 antagonizes histone deacetylase 7 thereby potentiating myocyte enhancer factor-2 in HeLa cells (Khurana et al., 2011).
ACTN4 product also is transcriptional co-activator of RelA/p65 subunit of NF-kB (Aksenova et al., 2013). Together with nuclear factor-Y, α-actinin 4 modulates transcription of CYP1A1, gene involved in pathogenesis of certain cases of lung and breast cancer (Poch et al., 2004).
α-Actinin 4 interacts with INO80 chromatin-remodeling complex and promote Cyclin B1 expression. In the mitotic phase, α-actinin 4 associates with upstream binding factor-dependent transcriptional complex (Kumeta et al., 2010).

iii/ Apoptosis. Endonuclease DNaseY is involved in apoptotic DNA degradation. α-Actinin 4 physically associates with DNaseY and dramatically enhances activity of the enzyme and percentage of PC12 cells developing apoptosis induced by teniposide (Liu et al., 2004).

iv/ Clathrin-mediated endocytosis. α-Actinin has been found in isolated plasma membranes containing clathrin (Burridge et al., 1980) and association of α-actinin 4 and clathrin heavy chain has been identified in prostate cancer cells. Overexpression of α-actinin 4 facilitated transferrin endocytosis (Hara et al., 2007).

v/ Function in glomerular podocytes. The presence of intact α-actinin 4 in the foot processes of podocytes is vital for the proper glomerular filtration. Elimination of the gene function in animal experiments (ACTN4 knockout mice) and mutations in human ACTN4 result in the development of focal segmental glomerulosclerosis (Kos et al., 2003; Kaplan et al., 2000).

vi/ Other. Exhaustive listing of α-actinin 4 interactions is beyond the scope of this structured review article. More details can be found at least in several excellent review publications (Sjöblom et al., 2008; Otey and Carpen, 2004; Oikonomou et al., 2011).