The noncanonical SMC protein Structural Maintenance of Chromatin flexible Hinge Domain containing 1 (Smchd1) is known to be essential for a variety of epigenetic silencing events through an unknown mechanism. It is required for the maintenance stage of X chromosome inactivation (XCI), and loss of function mutations in humans of the ATPase domain of SMCHD1 can cause Fascioscapulohumeral muscular dystrophy type 2 (FSHD2), while gain of function mutations in this region are associated with Bosma Arhinia Microphtalmia Syndrome (BAMS). Recent findings coupling Chromatin Immunoprecipitation (ChIP-seq) and Chromatin Conformation Capture (Hi-C) show that it may act by directing chromatin conformation, mediating long range interactions between discrete loci such as Hox clusters in mice (Jansz et al., Nature Structural & Molecular Biology 2018). Interestingly, Smchd1 also mediates chromatin interactions at olfactory receptor gene clusters. The olfactory receptor genes make up the largest mammalian gene family, but are very tightly regulated. They are only expressed in a handful of cell types in a monogenic and monoallelic fashion. We are currently focusing on the influence of Smchd1 on chromatin conformation and its effect on gene regulation at olfactory receptor gene cluster loci. By using genomic techniques in olfactory sensory neurons with wild-type, mutant and null Smchd1, and by testing the olfactory capabilities of mice with these different genetic backgrounds we hope to further our understanding of Smchd1’s role and mechanism in directing higher order chromatin structure and epigenetic regulation.