Purpose: The purpose of this study was to investigate the influence of sign characteristics in a key word signing (KWS) system on the functional use of those signs by adults with intellectual disability (ID). Method: All 507 signs from a Flemish KWS system were characterized in terms of phonological, iconic, and referential characteristics. Phonological and referential characteristics were assigned to the signs by speech-language pathologists. The iconicity (i.e., transparency, guessing the meaning of the sign; and translucency, rating on a 6-point scale) of the signs were tested in 467 students. Sign functionality was studied in 119 adults with ID (mean mental age of 50.54 months) by means of a questionnaire, filled out by a support worker. Results: A generalized linear model with a negative binomial distribution (with log-link) showed that semantic category was the factor with the strongest influence on sign functionality, with grammatical class, referential concreteness, and translucency also playing a part. No sign phonological characteristics were found to be of significant influence on sign use. Conclusion: The meaning of a sign is the most important factor regarding its functionality (i.e., whether a sign is used in everyday communication). Phonological characteristics seem only of minor importance.