The genome functions as an RNA factory that produces many structurally and functionally diverse transcripts. Circular RNA (circRNA) is a novel RNA transcript isoform, that remained elusive for decades until recent RNA-seq profiling demonstrates that they are differentially expressed in a regulated manner across diverse cell types. Of the thousands of known circRNA, few have been functionally characterised, and this makes them a functional enigma. Our work aims to uncover the functional significance of circRNAs by using a systematic high-throughput screening platform to interrogate their role in regulating cellular processes driven by the Wnt/beta-catenin signaling pathway. To do this, we first optimised the rules for shRNA targeting and suppression of individual circRNA, and based on these rules, generated a genome-wide (targeting ALL known circRNA) pooled shRNA lentiviral library (~40,000 shRNA), to study their loss-of-function consequences. We screened 18 mammalian cell lines that are either Wnt/beta-catenin dependent or independent and are derived from diverse cell lineages (colon, pancreas, skin and CNS). This allows us to cluster mutationally distinct cell lines and use proliferation as a phenotypic read out. Our results demonstrate two functional classes of circRNA, those that are required for proliferation in a context-independent manner i.e. in every cell line screened (cell essential). And, in a context-dependent manner i.e. required for proliferation in cells that are Wnt/beta-catenin dependent only (pathway-specific). In this work, we show that the finely tuned splicing and expression of circRNA has many potential functional roles in cellular processes which can be studied using systematic screening tools. CircRNAs add a circular dimension to the genomic regulation of cellular signaling pathways and this offers new avenues into understandiong the tight control of gene expression regulation in embryogenesis and its dysregulation in disease.