MPLKIP (M-phase specific PLK1 interacting protein) is an RNA metabolism factor essential for maintaining neuroectodermal tissue integrity. The protein localizes to the centrosome, midbody, and nucleus, where it interacts with core splicing factors and the lariat debranching enzyme DBR1 1. MPLKIP stabilizes DBR1 protein levels, which is critical for proper removal of introns from pre-mRNA and mRNA splicing 1. This RNA metabolic function is particularly important in highly differentiated tissues such as skin. Biallelic MPLKIP mutations cause trichothiodystrophy type 4 (TTD4), a rare autosomal recessive multisystem neuroectodermal disorder characterized by brittle hair with tiger-tail banding pattern, intellectual disability, nail dystrophies, ichthyosis, and susceptibility to infections 234. TTD4 is non-photosensitive, distinguishing it from other trichothiodystrophy forms 2. Disease-causing mutations reduce steady-state MPLKIP protein levels, compromising DBR1 stabilization and leading to impaired keratinocyte differentiation and an imbalanced proteome affecting skin development and immune function 1. Phenotypic manifestations extend to include cardiac involvement, with mitral regurgitation reported in some patients 5. Heterozygous carriers are typically asymptomatic, indicating autosomal recessive inheritance 3.