WT and mutant STAT3 are able to form homodimers and heterodimers. WT homodimers are phosphorylated downstream of cytokine receptor complexes and translocate to the nucleus where they act as transcription factors. In HIES, some mutant copes of STAT3 result in misfolded protein that are cleared together with any associated WT STAT3. HSPs are able to reverse this, restoring STAT3 function. mSTAT 3, mutant STAT3; pY, phosphorylated on tyrosine; SOCS3, suppressor of cytokine signaling 3; TRiC, tailless-complex polypeptide-1 ring complex.