Neurodegenerative diseasesNeurodegenerative disease encompass several neurological disorders such as prion diseasesPrion disease, synucleinopathiesSynucleinopathies, tauopathiesTauopathies, Huntington’s diseaseHuntington’s disease, amyotrophic lateral sclerosisAmyotrophic lateral sclerosis, and frontotemporal dementiaFrontotemporal dementia. Currently, definitive diagnosisDiagnosis of neurodegenerative diseases often requires postmortem detection of their characteristic misfolded protein aggregates in the central nervous system (CNS). Therefore, a pressing need exists to identify biomarkersBiomarkers of protein misfolding early using specimens outside the CNS. Human skinSkin is the body’s largest organ with extensive nerve innervation, allowing for easy punch biopsies to be collected premortem. Over the last few decades, extensive research has been done to search for skin biomarkers of misfolded protein aggregates for neurodegenerative diseases. Methodological developments to detect misfolded protein aggregates in the skin include conventional immunoassays and novel proteopathic seed amplification assays. Although still in its early stages, the diagnostic potential of skin biomarker assays has been demonstrated in a multitude of recent studies. The identification of biomarkers within easily accessible peripheral tissues, like the skin, would greatly improve the process of diagnosing these diseases, monitoring disease progression, and assessing the efficacy of clinical trials of potential therapeutic options. The following is an overview of the research in the ongoing investigation of skin biomarkersBiomarkers as viable indicators of neurodegenerative diseasesNeurodegenerative disease.