Steroid hormone receptors (SHRs) are shuttling proteins, which continuously undergo nuclear import and export. Although the various SHRs have different resting localizations in cells, rapid and almost complete nuclear translocation following ligand addition is a common behavior observed for almost all SHRs (except the already nuclear estrogen receptors). The Reactome event shows microtubule-associated nuclear translocation through the recruitment of the large immunophilin FKBP52 (FKBP4) to the SHR:HSP90 complex (Galigniana et al. 2002; Wochnik et al. 2005; Davies and Sanchez 2005; Galigniana MD et al. 2010). FKBP52 links glucocorticoid receptor (GR):HSP90 and mineralocorticoid receptor (MR):HSP90 complexes to dynein/dynactin motors favoring transport of the cytoplasmic SHR to the nucleus (Wochnik et al. 2005; Gallo L et al. 2007). Moreover, the cytoplasmic-nuclear movement of GR was blocked in fibroblasts co-expressing dynamitin, which dissociates dynein from its cargoes (Harrell et al. 2004). FKBP52 directly binds to the motor protein dynein through the peptidyl-prolyl isomerase (PPIase) domain (Wochnik et al. 2005). Interestingly, the PPIase domain of another immunophilin FKBP51 (FKBP5) is unable to interact with dynein. Without hormone, FKBP51 is the major immunophilin in GR:HSP90 complexes, whereas after hormone treatment, FKBP52 rapidly replaces FKBP51 such that these complexes are now able to translocate to the nucleus with an accelerated rate (Davies et al. 2002). In addition, replacement of FKPB52 by FKBP51 favored the cytoplasmic localization of MR (Galigniana MD et al. 2010). On the other hand, GR was apparently able to translocate to the nucleus with the same rate even if the microtubule network was completely disrupted suggesting that he subcellular localization of SHRs can be controlled by several coexisting mechanisms (Czar et al. 1995). Indeed, in yeast and mammalian cells liganded and unliganded SHRs can bind several importins to be translocated into the nucleus (Freedman & Yamamoto 2004; Picard & Yamamoto 1987). In addition, importin beta and the integral nuclear pore glycoprotein NUP62 interact with HSP90, HSP70, p23, and the TPR domain proteins FKBP52 and PP5. NUP62 and GR are able to interact in a more efficient manner when chaperoned by the HSP90-based heterocomplex (Echeverria et al. 2009). GR cross-linked to the HSP90 heterocomplex is able to translocate to the nucleus in digitonin-permeabilized cells treated with steroid, suggesting that GR could pass through the pore in its untransformed state (Echeverria et al. 2009).