An entire clan built from inbreeding, brothers Liam and Ryan proudly express their incestuous relationship with each other, along with their deaf-mute sister, Margaret.
They have numerous other siblings and family members numbering to about 14, all of whom show the distinctive McPoyle trait which is composed of uni-brows and eczema. They also have a brother named Doyle who is an aspiring football player. ("The Gang Gets Invincible")
They are enemies with Charlie for foiling their plan to profit from a bogus molestation lawsuit against the school district ("Charlie Got Molested"), and with the rest of The Gang for ruining Doyle's chance of playing for the Philadelphia Eagles when Frank accidentally shoots him in the leg. ("The Gang Gets Invincible")
A conflict arose between Ryan and Liam when the latter decided to get engaged to Maureen Ponderosa. An unacceptable decision to his brother given that their bloodline has been kept "pure and clean for a thousand years." The two eventually make up when Liam reveals his true motive for marrying Maureen, which is to taint the blood of others and allow the McPoyles to take over the world. Unfortunately, the plan never came to fruition as Maureen's brother, Bill, spikes the milk with bath salts and turn the McPoyle clan into flesh eating zombie-like creatures. In the end, Liam gets his right eye ripped out and eaten.("The Maureen Ponderosa Wedding Massacre")
The brothers then try their hand on entrepreneurship and invested in a video renting store, which they believe to be an emerging market. When Dennis and Mac drop by to rent a movie, they vehemently deny them service as they hold them responsible for the loss of Liam's eye. This form of leverage gets them invited to the gang's Thanksgiving Party which was a well meaning but poorly executed attempt to "squash their beef" with the people they have hurt. The brothers agree to attend expecting to get an eye, or at the very least an apology. But instead, they were locked in the apartment with the other attendees during a food fight, while unbeknownst to them, a fire had started in Mac's room.