Other ; Many diseases present with distinct phenotypes, making descriptions of phenotypes valuable for identifying and diagnosing human diseases. The Human Phenotype Ontology (HPO) was developed to provide a structured vocabulary containing textual and logical descriptions of human phenotypes. The HPO is used for phenotype-genotype alignment in systems like the Monarch Initiative to provide disorder prediction, variant prioritization, and patient matching between known diseases and model organisms. Here we describe recent work to extend the utility of the HPO through the systematic addition of approximately 6,000 synonyms. Until now, most of the HPO synonyms were composed of clinical terms unfamiliar to patients. For example, a patient may know they are ‘color-blind’, but may not be familiar with its official phenotype term ‘Dyschromatopsia’. Therefore, our goals is to add synonyms in “layperson-ese” so that HPO can be used by patients as well as basic research scientists and clinicians to help improve disease characterization and diagnosis. We systematically reviewed current HPO classes (approximately 12,000) and assigned layperson synonyms to each class where applicable. The layperson synonyms refer to colloquial terms used to describe phenotypic features associated with medical conditions. Each layperson synonym was annotated to indicate its special status, then classified as either exact (precise); broad (more general); narrow (more specific); or related (associated). The review process included various methods of identifying and validating possible layperson synonyms. We first queried the HPO to avoid duplicate terms. We then batched similar kinds of terms together, such as those related to bone abnormalities, to maintain consistent synonym terminology. For example, the phenotypes of the femur were assigned layperson synonym ‘of thigh bone’ and morphological abnormalities were described as ‘abnormal shape of ’. We consulted online resources (e.g., Wikipedia, Mayo Clinic) as well as specialized resources (e.g., Uberon, Gene Ontology) to find additional synonyms. As a quality control measure, we reviewed each other’s work, consulted with clinical experts when necessary, and queried Google for the assigned layperson term to verify that it retrieved the appropriate medical term and was in use. Some challenges of assigning layperson synonyms involved reconciling lay terms with the logic and structure of the HPO and determining the best mechanism to validate the lay synonyms. Additionally, not every term has a lay synonym or it may already exist in the HPO, such as ‘widow’s peak’ or ‘hitch hiker’s thumb’. Finally, some terms have complicated medical terminology, like ‘short distal phalanx of first finger’, for which a single layperson term is difficult to establish without using the definition of the term. The addition of layperson synonyms increases the usability of the HPO, making it useful for data interoperability across clinicians and patients. Additionally, this work will enable crowdsourcing by citizen scientists. The layperson synonyms are available in the latest release of theHPO.