FKBP5 and glucocorticoid resistance: One of the target genes is FKBP5, and its transcriptional activation by the GR dimer creates a negative feedback loop, whereby hypercortisolemia and glucocorticoid resistance can be attributed to the excess FKBP5 protein that has enhanced affinity for the glucocorticoid receptor (Scammell et al., 2001).