While actin was discovered in the nucleus over 50 years ago, research lagged for 
decades due to strong skepticism. The revitalization of research into nuclear 
actin occurred after it was found that cellular stresses induce the nuclear 
localization and alter the structure of actin. These studies provided the first 
hints that actin has a nuclear function. Subsequently, it was established that 
the nuclear import and export of actin is highly regulated. While the structures 
of nuclear actin remain unclear, it can function as monomers, polymers, and even 
rods. Furthermore, even within a given structure, distinct pools of nuclear 
actin that can be differentially labeled have been identified. Numerous 
mechanistic studies have uncovered an array of functions for nuclear actin. It 
regulates the activity of RNA polymerases, as well as specific transcription 
factors. Actin also modulates the activity of several chromatin remodeling 
complexes and histone deacetylases, to ultimately impinge on transcriptional 
programing and DNA damage repair. Further, nuclear actin mediates chromatin 
movement and organization. It has roles in meiosis and mitosis, and these 
functions may be functionally conserved from ancient bacterial actin homologs. 
The structure and integrity of the nuclear envelope and sub-nuclear compartments 
are also regulated by nuclear actin. Furthermore, nuclear actin contributes to 
human diseases like cancer, neurodegeneration, and myopathies. Here, we explore 
the early discovery of actin in the nucleus and discuss the forms and functions 
of nuclear actin in both normal and disease contexts. Anat Rec, 301:1999-2013, 
2018. © 2018 Wiley Periodicals, Inc.