biostudies-literatureHeissler SMNational Institute of General Medical SciencesNIGMS NIH HHS468-482https://www.ebi.ac.uk/biostudies/studies/S-EPMC11796330biostudies-literatureUnknown292(3)Actin is a highly conserved and fundamental protein in eukaryotes and participates in a broad spectrum of cellular functions. Cells maintain a conserved ratio of actin isoforms, with muscle and non-muscle actins representing the main actin isoforms in muscle and non-muscle cells, respectively. Actin isoforms have specific and redundant functional roles and display different biochemistries, cellular localization, and interactions with myosins and actin-binding proteins. Understanding the specific roles of actin isoforms from the structural and functional perspective is crucial for elucidating the intricacies of cytoskeletal dynamics and regulation and their implications in health and disease. Here, we review how the structure contributes to the functional mechanisms of actin isoforms with aThe FEBS journalStructural and functional mechanisms of actin isoforms.PMC11796330R01 GM143414R01GM143539R01 GM143539R01GM143414Chinthalapudi KHeissler SMfalseStructural and functional mechanisms of actin isoforms.Actin is a highly conserved and fundamental protein in eukaryotes and participates in a broad spectrum of cellular functions. Cells maintain a conserved ratio of actin isoforms, with muscle and non-muscle actins representing the main actin isoforms in muscle and non-muscle cells, respectively. Actin isoforms have specific and redundant functional roles and display different biochemistries, cellular localization, and interactions with myosins and actin-binding proteins. Understanding the specific roles of actin isoforms from the structural and functional perspective is crucial for elucidating the intricacies of cytoskeletal dynamics and regulation and their implications in health and disease. Here, we review how the structure contributes to the functional mechanisms of actin isoforms with a2025-01-01T00:00:00Z2025 Feb2026-06-02T10:17:13.943Z2025-04-04T07:26:49.618ZS-EPMC117963303877998710.1111/febs.17153