NAP1L4 encodes a nucleosome assembly protein that plays a general and integral role in chromatin remodeling, a fundamental epigenetic mechanism that regulates gene expression (Rodriguez et al., 1997) (Fig. 1 and Table 3). Specifically, nucleosome assembly proteins, such as NAP1L4, can function to recruit histones, chromatin remodeling complexes (i.e., SWI/SNF or ACF), or transcription factors which all work to regulate gene expression (Park and Luger, 2006b). Noteworthy is the observation that the NAP1 gene family (NAP1L1–1L5) appears to be exclusively expressed in brain compared to other families of nucleosome assembly proteins (Park and Luger, 2006a). There is a growing literature demonstrating that addiction to drugs and alcohol alters chromatin remodeling mechanisms, including alterations in nucleosome assembly, in neurons which generates massive gene expression dysregulation leading to altered synaptic plasticity and ultimately behavioral dysfunction (Medrano-Fernandez and Barco, 2016; Robison and Nestler, 2011; Vogel-Ciernia and Wood, 2014). For example, alcohol dependence is mechanistically associated with altered chromatin remodeling that leads to alcohol withdrawal induced anxiety, a phenotype arising in part from altered synaptic plasticity in limbic regions of the brain (Krishnan et