The regulation of gene expression by thyroid hormone (T3) involves binding of the hormone to nuclear receptors (TR) acting as T3-dependent transcription factors encoded by TR (NR1A1) and TR (NR1A2) genes. Several thyroid hormone receptor variants have already been characterized, but only some of them display T3 binding activity. In this study, we have identified another transcript, TR-E6, produced by alternative splicing with micro-exon 6b instead of exon 6. This splicing leads to the synthesis of a protein devoid of a hinge domain. The TR-E6 transcript is detected in all mouse tissues tested. Though TR-E6 did not bind DNA its expression induced a TR1 sequestration in the cytoplasm. Functional studies demonstrated that TR-E6 inhibits the transcriptional activity of TR1 and RXR, but not of RAR. We also found that TR-E6 efficiently decreased the ability of TR to inhibit MyoD transcriptional activity during myoblast proliferation. Consequently, when overexpressed in myoblasts, it stimulated terminal differentiation. We suggest that this novel TR variant may act as down regulator of overall T3 receptor activity, including its ability to repress myoD transcriptional activity during myoblast proliferation.