White matter diseases comprise a very broad differential diagnosis. Subcortical U-fibers are known as short association fibers and have unique features. We aim to familiarize radiologists with identifying the presence or absence of subcortical U-fiber involvement.

•Anatomical and pathological features of subcortical U-fibers•Radiologic pattern of white matter disease•Cases in which subcortical U-fibers are generally spared-Chronic small-vessel ischemic disease-Delayed post-hypoxic leukoencephalopathy-Post-radiation therapy•Cases in which subcortical U-fibers are preferentially affected1. Autoimmune/demyelinating-Progressive multifocal leukoencephalopathy (PML) -Multiple sclerosis (MS)-Acute disseminated encephalomyelitis (ADEM) 2. Metabolic-Wilson disease-Kearns-Sayre syndrome/chronic progressive external ophthalmoplegia -L-2 hydroxyglutaric aciduria 3. Vascular-Posterior reversible encephalopathy syndrome (PRES)-ECMO-related multiple microbleeds (COVID-19 case) 4. Neurodegenerative-Neuronal intranuclear inclusion disease (NIID)